A new recommendation from the Organisation for Economic Co-operation and Development (OECD) calls on member governments to harmonise their procedures for the oversight and management of clinical trials along risk-based lines, to help overcome significant barriers to international non-commercial studies.

The 2012 OECD Recommendation on the Governance of Clinical Trials and an accompanying Explanatory Memorandum were developed by the Organisation’s Global Science Forum following a year of consultations and “intensive” work by an expert group led by Professor Jacques Demotes, director of the European Clinical Research Infrastructure Network, as well as Professor Yuji Sato (Japan) and Dr Mary Smolskis (United States).

The Recommendation was adopted by the OECD Council after being reviewed by the Global Science Forum and the Committee on Scientific and Technological Policy.

It serves as a policy instrument setting out a new framework to align the cross-border oversight of clinical trials, while the Explanatory Memorandum provides the background and the context for the Recommendation, as well as “concrete information for facilitating the implementation of the principles contained in the Recommendation”.

Improving consistency

The main focus, the Memorandum explains, is “on improving consistency among national regulations and their interpretations, and on streamlining procedures for the oversight and management of clinical trials, by introducing a proportionate regulatory approach, while enhancing the protection of participants in research trials”.

The OECD Council recommends specifically that members should “adapt their national regulations and procedures to incorporate a risk-based methodology for the oversight and management of clinical trials, taking into account the principles set out in the Annex to this Recommendation”.

In doing so it recognises, inter alia, that many clinical trials are driven by pressing public health needs in areas “where diseases and conditions affect only a small number of patients worldwide, or where treatments are not commercially viable, or where trials aim to improve existing procedures and prescribing practices”.

These trials increasingly involve multi-site international collaboration. However, differences in national and regional regulations, as well as their interpretation, have resulted in highly complex administrative processes – especially for multinational trials, the Council points out.

National regulations that adopt these uniform approaches regardless of the risk involved and the research objective “may hamper the development of clinical trials, particularly those sponsored by non-profit groups such as universities, hospitals and charities”, it adds.

Cross-border trend

The Explanatory Memorandum highlights the growing trend to perform large-scale clinical trials across borders, to the extent that in the EU nearly 25% of all trial applications are now for multinational studies.

Moreover, cross-border trials account for some two-thirds of all subjects enrolled in studies, “so mono-national clinical trials are now largely limited to small studies with low recruitment targets”.

While international collaboration brings many advantages, such as faster patient recruitment and more widely applicable trial outcomes, multinational clinical trials are “significantly more complex to perform than national ones due in particular to the difficulties arising from the diversity of legal frameworks”, the Memorandum notes.

Pharma advantage

In large pharmaceutical companies, it adds, this complexity is “usually managed by the in-house regulatory affairs departments. Furthermore, large companies often have subsidiaries in the different countries where trials are being performed, giving them access to local information and expertise”.

In addition, the industry can afford to outsource trials to contract research organisations, an option seldom available to academic sponsors working on tight budgets.

Although the OECD’s Recommendation is “primarily driven by the need to facilitate co-operation among academic groups for clinical trials undertaken for non-profit purposes”, the Council does nonetheless suggest that member governments “may wish to extend the implementation of this Recommendation to the oversight and management of all clinical trials”.

Risk consensus

As the Memorandum acknowledges, an international regulatory framework harmonised on risk-management principles calls for “consensus on a number of key issues such as how to define the risk, which institution should be in charge of defining and validating potential risk categories, and which existing regulatory and monitoring processes would be affected”.

While there is broad consensus among stakeholders on adopting a risk-based approach to the regulation of clinical trials, the OECD Council says, to date there has been no mechanism that “would help align the regulatory requirements for clinical trials worldwide, and to develop and validate the risk assessment tools and risk-adapted monitoring procedures needed for its use in international clinical trials”.

The OECD’s Recommendation “provides such a mechanism”, it adds.

The risk-assessment principles underlying the Recommendation combine:

• a “stratified approach, generally based on the marketing authorisation status of the medical product, that can be applied in legislation or regulation in a common manner across countries” with

• a trial-specific approach that “considers a large number of other issues such as additional diagnostic procedures, specific populations concerned, or informed consent”.

The OECD’s Committee for Scientific and Technological Policy will monitor the implementation of the Recommendation, review it in light of its impact on the quality of clinical trials and on the safety of clinical-trial participants, and report back to Council within four years of adoption “and as appropriate thereafter”.